Role of the immunoproteasome in the pathogenesis of metabolic syndrome
Project/Area Number |
23591359
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Endocrinology
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Research Institution | Jichi Medical University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
TAKAHASHI Masafumi 自治医科大学, 医学部, 教授 (40296108)
|
Project Period (FY) |
2011-04-28 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 免疫プロテアソーム / 肥満 / 高脂肪食 / 炎症 / マクロファージ / メタボリックシンドローム / メタボリック症候群 / 内臓脂肪 / 脂肪肝 / 動脈硬化 |
Outline of Final Research Achievements |
Obesity increases the risk of developing metabolic disorders. The detailed pathogenic mechanism of inflammation in obesity is not fully understood. Low-molecular-mass polypeptide-7 (LMP7) is a proteolytic subunit of the immunoproteasome that plays a fundamental role in the immune system, and has been involved in the pathogenesis of several autoimmune diseases. We investigated the role of LMP7 in obesity using LMP7-deficient mice. LMP7 deficiency showed resistance to obesity, suppressed macrophage accumulation in adipose tissue, improved glucose tolerance, and suppressed serum triglyceride level elevation induced by high-fat diet (HFD) feeding, which increased fecal lipid contents. Using bone-marrow-transferred chimeric mice, we found that LMP7 in both hematopoietic and non-hematopoietic cells had critical roles in HFD-induced obesity development. These findings demonstrate that LMP7 in both hematopoietic and non-hematopoietic cells contributes to the pathogenesis of obesity.
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Report
(5 results)
Research Products
(26 results)
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[Journal Article] NLRP3 protein deficiency exacerbates hyperoxia-induced lethality through Stat3 protein signaling independent of interleukin-1β2015
Author(s)
Mizushina Y, Shirasuna K, Usui F, Karasawa T, Kawashima A, Kimura H, Kobayashi M, Komada T, Inoue Y, Mato N, Yamasawa H, Latz E, Iwakura Y, Kasahara T, Bando M, Sugiyama Y, Takahashi M
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Journal Title
J Biol Chem
Volume: 290
Issue: 8
Pages: 5065-5077
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages2014
Author(s)
Hara K, Shirasuna K, Usui F, Karasawa T, Mizushina Y, Kimura H, Kawashima A, Ohkuchi A, Matsuyama S, Kimura K, Takahashi M
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Journal Title
PLoS One
Volume: 9
Issue: 12
Pages: 1-17
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inflammasome activation by mitochondrial oxidative stress in macrophages leads to the development of angiotensin II-induced aortic aneurysm2014
Author(s)
Usui F, Shirasuna K, Kimura H, Tatsumi K, Kawashima A, Karasawa T, Yoshimura K, Aoki H, Tsutsui H, Noda T, Sagara J, Taniguchi S, Takahashi M
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Journal Title
Arterioscler Thromb Vasc Biol
Volume: 35
Issue: 1
Pages: 127-136
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Nanosilica-induced placental inflammation and pregnancy complications: Different roles of the inflammasome components NLRP3 and ASC2014
Author(s)
Shirasuna K, Usui F, Karasawa T, Kimura H, Kawashima A, Mizukami H, Ohkuchi A, Nishimura S, Sagara J, Noda T, Ozawa K, Taniguchi S, Takahashi M
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Journal Title
Nanotoxicology
Volume: 11
Pages: 1-14
Related Report
Peer Reviewed
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[Journal Article] NLRP3 Regulates Neutrophil Functions and Contributes to Hepatic Ischemia-Reperfusion Injury Independently of Inflammasomes.2014
Author(s)
Inoue Y, Shirasuna K, Kimura H, Usui F, Kawashima A, Karasawa T, Tago K, Dezaki, Nishimura S, Sagara J, Noda T, IwakuraY, Hiroko Tsutsui H, Taniguchi S, Yanagisawa K, Yada T, Yasuda Y, Takahashi M.
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Journal Title
J Immunol
Volume: 192(9)
Issue: 9
Pages: 4342-4351
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] ASC in Renal Collecting Duct Epithelial Cells Contributes to Inflammation and Injury after Unilateral Ureteral Obstruction2014
Author(s)
Komada T, Usui F, Shirasuna K, Kawashima A, Kimura H, Karasawa T, Nishimura S, Sagara J, Noda T, Taniguchi S, Muto S, Nagata D, Kusano E, Takahashi M
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Journal Title
American Journal of Pathology
Volume: 184(5)
Issue: 5
Pages: 1287-1298
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhibition of Fas ligand in NOD mice unmasks a protective role for IL-10 against insulitis development.2011
Author(s)
Xiao Z, Mohamood AS, Uddin S, Gutfreund R, Nakata C, Marshall A, Kimura H, Caturegli P, Womer KL, Huang Y, Jie C, Chakravarti S, Schneck JP, Yagita H, Hamad AR.
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Journal Title
American Journal of Pathology
Volume: 178
Pages: 725-732
Related Report
Peer Reviewed
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